Invariant Natural Killer T Cells(Beijing YouAn Hospital)(Invariant Natural Killer T Cells(Beijing YouAn Hospital))

概要

基本信息

药物类型

恒定自然杀伤T

别名

iNKT Cells

靶点-

作用方式-

作用机制

免疫细胞毒性、自然杀伤细胞替代物

治疗领域

在研适应症

非在研适应症

原研机构

在研机构

非在研机构-

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)临床2期

特殊审评-

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关联

3

项与 Invariant Natural Killer T Cells(Beijing YouAn Hospital) 相关的临床试验

ChiCTR2200059194

/ Suspended早期临床1期IIT

Study of lenvatinib combined with iNKT cell immunotherapy for advanced hepatocellular carcinoma

开始日期2022-01-05

申办/合作机构-

NCT04011033

/ Completed临床2期IIT

Study of Adoptive Transfer of Invariant Natural Killer T Cells Combined With TAE/TACE to Treat Unresectable Hepatocellular Carcinoma (HCC): Phase II Clinical Trial

Hepatocellular carcinoma (HCC) is a common disease with high mortality. More than 80% patients receive a diagnosis when their tumors are too advanced for curative approaches and have a dismal prognosis. invariant Natural Killer T (iNKT) cell exhibit antitumor activity against malignant tumors through producing high levels of cytokines. iNKT cells are abundant in the liver, but their function is defective in liver cancer. After expansion and restored function in vitro, iNKT cells can home to liver, then they play key antitumor function. We have finished a phase I study of adoptive transfer of autologous iNKT cells for treating patients with unresectable HCC. Safety and feasibility of iNKT infusion was proved. The purpose of this study was to verify the effectiveness of iNKT cell infusion in patients with unresectable HCC who had previously failed transcatheter arterial embolization (TAE) / transcatheter arterial chemoembolization (TACE).

开始日期2018-03-01

申办/合作机构

首都医科大学附属北京佑安医院

[+1]

NCT03175679

/ Completed临床1期IIT

A Study of Adoptive Invariant Nature Killer T Cell Therapy for Relapsed/Advanced Hepatocellular Carcinoma (HCC)

This study enrolls patients who have relapsed/advanced hepatocellular carcinoma (HCC, BCLC stage C). The HCC tumor relapsed or metastasized through the body after standard treatment or the patients cannot receive standard treatment under current conditions. This research study uses special immune system cells called iNKT cells, a new experimental treatment.
The purpose of this study is to find the biggest dose of iNKT cells that is safe and tolerance, to see how long they last in the body, to learn the immunoresponse in the body, to learn the side effects are and to see if the iNKT cells will help people with relapsed/advanced hepatocellular carcinoma (HCC).

开始日期2017-04-01

申办/合作机构

首都医科大学附属北京佑安医院

100 项与 Invariant Natural Killer T Cells(Beijing YouAn Hospital) 相关的临床结果

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100 项与 Invariant Natural Killer T Cells(Beijing YouAn Hospital) 相关的转化医学

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100 项与 Invariant Natural Killer T Cells(Beijing YouAn Hospital) 相关的专利（医药）

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44

项与 Invariant Natural Killer T Cells(Beijing YouAn Hospital) 相关的文献（医药）

2023-06-01·Cancer research communications

Safety and Clinical Response to Combined Immunotherapy with Autologous iNKT Cells and PD-1⁺CD8⁺ T Cells in Patients Failing First-line Chemotherapy in Stage IV Pancreatic Cancer.

Article

作者: Xu, Jianqing ; Zhang, Wei ; Jin, Yanling ; Mao, Xiaoting ; Yan, Jia ; Wang, Jing ; Hu, Huiliang ; Cheng, Xiaobo ; Zhou, Liting ; Zhang, Xiaoyan ; Qin, Ran ; Xia, Bili

PurposeA phase I clinical trial was conducted to assess the safety and feasibility of invariant natural killer T (iNKT) cells combined with PD-1⁺CD8⁺ T cells in patients with advanced pancreatic cancer and failing the first-line chemotherapy.Patients and MethodsFifteen eligible patients were enrolled, of whom 9 received at least three cycles of treatment each. In total, 59 courses were administered.ResultsFever was the most common adverse event, peaking at about 2-4 hours after cell infusion and reverting within 24 hours without treatment in all patients. Influenza-like reactions such as headache, myalgia, and arthralgia were also observed in 4, 4, and 3 of the patients, respectively. In addition, vomiting and dizziness were prevalent, while abdominal pain, chest pain, rash, and stuffy nose were rare adverse events, each reported in 1 patient. Side effects above grade 2 were not observed. Two patients achieved partial regression, while 1 patient experienced disease progression assessed 4 weeks after the third course. Three patients are still alive at the time of writing and have progression-free survival longer than 12 months. The overall survival time has been extended to over 12 months in 6 of the 9 patients. No constant changes of CD4⁺ T, B, and NK cells were recorded except for elevated CD8⁺ T cells after the first course.ConclusionsThe combination of autologous iNKT cells and PD-1⁺CD8⁺ T cells was a safe therapeutic strategy against advanced pancreatic cancer. The patients exhibited a potentially promising prolonged survival time. Further study appears warranted to evaluate the efficacy of these combined cell infusions in pancreatic cancer.Trial registrationThis trial was included in the clinical trial which was registered in ClinicalTrials.gov (ID:NCT03093688) on March 15, 2017.SignificanceThere is an unmet need for novel, more effective, and tolerable therapies for pancreatic cancer. Here we present a phase I clinical trial employing iNKT cells combined with PD-1⁺CD8⁺ T cells in 9 patients with advanced pancreatic cancer and failing the first-line chemotherapy. The combined immunotherapy was shown to be feasible in the enrolled patients with limited side effects and optimistic clinical responses, which could bring opportunity of therapeutic advancement.

2023-02-15·Cancer Research

Long-Chain Acylcarnitines Induce Senescence of Invariant Natural Killer T Cells in Hepatocellular Carcinoma

Article

作者: Chen, Yiqing ; Zhu, Rongfei ; Weng, Xiufang ; Tan, Xiaosheng ; Liang, Zhihui ; Zhang, Ziyao ; Cheng, Xue ; Li, Mingyu ; Wu, Mi ; Zhu, Peng ; Wang, Wei ; Wu, Xiongwen

AbstractCD1d-restricted invariant natural killer T (iNKT) cells actively patrol the liver and possess valuable antitumor potential. However, clinical trials evaluating administration of iNKT cell–specific agonist α-galactosylceramide (α-GalCer) have failed to achieve obvious tumor regression. Improving the efficacy of iNKT cell–based immunotherapy requires a better understanding of the factors restraining the clinical benefits. In the context of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), we found circulating and hepatic iNKT cells were hyperactivated but demonstrated imbalances in ratio and defective α-GalCer responsiveness. Exogenous IL2 helped to expand residual α-GalCer–responsive clones with reduced T-cell receptor diversity. However, transcriptome-wide analysis revealed activation of the senescence-associated secretory phenotype and dampened cytotoxicity in iNKT cells, weakening their immune surveillance capacity. The senescent status of iNKT cells from the patients was further illustrated by cell-cycle arrest, impaired telomere maintenance, perturbed calcium transport-related biological processes, and altered metabolism. Lipidomic profiling revealed the accumulation of long-chain acylcarnitines (LCAC) and aberrant lipid metabolism in HCC tissue. Exogenous LCACs, especially palmitoyl-carnitine and stearoyl-carnitine, inhibited iNKT cell expansion and promoted senescence. Collectively, our results provide deeper insights into iNKT cell dysregulation and identify a cell senescence–associated challenge for iNKT cell–based immunotherapy in HBV-related HCC. The mechanistic links between iNKT cell senescence and accumulated LCACs suggest new targets for anti-HCC immunotherapies.Significance:Patients with HBV-related HCC exhibit a cell senescence–associated dysregulation of invariant natural killer cells that is related to altered lipid metabolism and accumulated LCACs in tumor tissue.

2023-01-01·Journal of hepatocellular carcinoma

Efficacy of Invariant Natural Killer T Cell Infusion Plus Transarterial Embolization vs Transarterial Embolization Alone for Hepatocellular Carcinoma Patients: A Phase 2 Randomized Clinical Trial.

作者: Xiong, Fang ; Liu, Fuquan ; Guo, Jiang ; Bao, Xuli ; Lu, Jun ; Guo, Jia ; Wu, Yifan

PurposeInvariant NKT cells (iNKT) are CD1d-restricted T cells with the capacity of antitumor immunity. The safety of autologous iNKT cell treatment in hepatocellular carcinoma (HCC) has been verified. This study aimed to investigate its efficacy in advanced HCC after transarterial chemoembolization (TACE) failure.Patients and methodsThis open-label, randomized, controlled, trial enrolled 60 patients with unresectable HCC after TACE failure at three centers. Transarterial embolization (TAE) was used instead of TACE to protect iNKT cell function. Patients were randomly assigned (1:1) to receive TAE therapy with (TAE-iNKT) or without (TAE) biweekly iNKT cell infusion. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), quality of life (QoL), peripheral blood cell count, and safety.ResultsFifty-four patients completed the study. Median PFS was significantly higher in TAE-iNKT patients (5.7 months [95% CI, 4.3-7.0 months]) compared with TAE patients (2.7 months [95% CI, 2.3-3.2 months]; hazard ratio 0.32 [95% CI, 0.16-0.63]; P<0.001). Higher ORR and DCR were observed in TAE-iNKT patients (52% and 85%, respectively) compared with TAE patients (11% and 33%; respectively). Five TAE-iNKT patients and 1 TAE patient achieved completed response. The median time to deterioration in QoL was longer in TAE-iNKT patients (9.2 months [95% CI, 6.0-13.3 months]) compared with TAE patients (3.0 months [95% CI, 2.9-3.0 months]). The mean lymphocytes were higher in the TAE-iNKT group than in the TAE group at 8 (1.48 vs 0.95×10⁹/L, P = 0.007) and 12 (1.49 vs 0.89×10⁹/L, P = 0.001) weeks. Grade 3 adverse events occurred in 1 TAE-iNKT patient (4%) and 5 TAE patients (19%). All the other adverse events were grade 1-2.ConclusioniNKT cell infusion significantly improved PFS, ORR, DCR, and QoL with manageable toxicity during TAE therapy in patients with HCC. Trial Registration ClinicalTrials.gov Identifier: NCT04011033.

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
不可切除的肝细胞癌	临床2期	中国	首都医科大学附属北京佑安医院	2018-03-01
复发癌	临床前	中国	首都医科大学附属北京佑安医院	2017-04-01

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04011033 (Phase 2 Randomized Clinical Trial \| 593, CTgov)	临床2期	不可切除的肝细胞癌	60	Human recombinated Interleukin-2+iNKT cells (TAE/TACE+iNKT for Unresectable HCC)	(齋選獵蓋膚膚衊餘憲積) = 遞壓膚願膚鏇獵襯鏇構齋壓遞夢願積糧鬱窪艱 (蓋窪遞艱蓋鏇獵鬱衊膚, 鑰積鏇獵鹽襯糧壓簾壓 ~ 獵襯鏇齋獵廠餘構夢餘) 更多	-	2024-10-08
				TACE (TAE/TACE for Unresectable HCC)	(齋選獵蓋膚膚衊餘憲積) = 襯齋衊願獵鹽築積築鑰齋壓遞夢願積糧鬱窪艱 (蓋窪遞艱蓋鏇獵鬱衊膚, 醖鏇鬱齋鏇顧簾醖積範 ~ 範艱範艱鹹遞鏇築鬱糧) 更多
NCT03175679 (CTgov)	临床1期	肝细胞癌 \| 复发癌	10	IL-2+Tegafur+iNKT cells (iNKT Cell Loading Dose:3x10^7/m2)	繭築膚製願簾鹹繭顧繭(壓製製糧齋廠構觸淵網) = 鑰築顧廠艱鹽衊網鏇壓齋憲鏇觸廠鬱膚衊齋鏇 (衊齋廠艱衊餘鹽觸糧衊, 憲醖蓋積艱衊壓築觸蓋 ~ 衊醖製餘構遞壓壓構餘) 更多	-	2024-09-19
				IL-2+Tegafur+iNKT cells (iNKT Cell Loading Dose:6x10^7/m2)	繭築膚製願簾鹹繭顧繭(壓製製糧齋廠構觸淵網) = 衊構願選壓積鏇蓋築憲齋憲鏇觸廠鬱膚衊齋鏇 (衊齋廠艱衊餘鹽觸糧衊, 觸窪製衊餘鏇範壓憲衊 ~ 願鹽齋窪築餘鑰糧選鏇) 更多